Previous work from this laboratory has documented deficiencies of the cell mediated immune response in human and experimental murine leprosy. In recent publications, we have demonstrated a perturbation of lymphocyte recirculation in M. lepraemurium infected rats after intravenous infusion of syngeneic, radioactively labelled thoracic duct cells from normal animals. We have also studied the kinetic of lymphocyte mobilization by the synthetic polyanion, polymethacrylic acid (PMAA), in both normal and leprous rodents. In infected animals, mobilization of lymphocytes by PMAA was found to be significantly less than normal, thus providing further evidence for the perturbation of lymphocyte traffic caused by the granulomatous infection of lymphoid organs. Currently, our laboratory is studying the nature of immunosuppressor activity that is generated within the spleens of mice with M. lepraemurium infection. To date we have found that from the 5th through 10th wk after inoculation, spleen cells from infected mice mildly but reproducibly suppress the direct plaque forming cell response of normal spleen cell cultures to sheep erythrocytes. Severe immunodepression by infected spleen cells at 10-11 wk was associated with the onset of rapid splenic enlargement and a loss of cutaneous delayed-type hypersensitivity to antigens of M. lepraemurium. The nature of the spleen cells mediating immunosuppressor activity is currently under active investigation. We will also seek to determine whether suppressor cells from infected animals are capable of suppressing the T-dependent antibody response to TNP-LPS and DNP-Ficoll. Recently, we have determined that suppressor spleen cells generate a soluble suppressor factor. The nature of this factor(s) and the cell or cells or origin will be explored further.